Mycobacterium Tuberculosis Lysine-Ɛ-Aminotransferase A Potential Target In Dormancy: Benzothiazole Based Inhibitors

Keywords

3D granuloma model; Benzothiazole derivatives; Dormancy; Lysine-ɛ amino transferase; Mycobacterium tuberculosis

Abstract

MTB lysine-ɛ-aminotransferase (LAT) was found to play a crucial role in persistence and antibiotic tolerance. LAT serves as a potential target in the management of latent tuberculosis. In present work we attempted to derivatize the benzothiazole lead identified through high throughput virtual screening of Birla Institute of Technology and Science in house database. For Structure activity relationship purpose 22 derivatives were synthesized and characterized. Among synthesized compounds, eight compounds were found to be more efficacious in terms of LAT inhibition when compared to lead compound (IC50 10.38 ± 1.21 µM). Compound 22 exhibits bactericidal action against nutrient starved Mycobacterium tuberculosis (MTB). It also exhibits significant activity in nutrient starvation model (2.9 log folds) and biofilm model (2.3 log folds).

Publication Date

1-1-2017

Publication Title

Bioorganic and Medicinal Chemistry

Volume

25

Issue

10

Number of Pages

2761-2771

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.bmc.2017.03.053

Socpus ID

85017402174 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85017402174

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